Side Effects News & Reports

Attorney Tom Lamb started practicing law in 1988. He has been representing patients and their families in drug injury lawsuits as his primary practice area for the past 18 years. For more legal and medical information about drug side effects cases, visit our website: DrugInjuryLaw.com

In February 2018 the United States Judicial Panel on Multidistrict Litigation (JPML) established MDL No. 2809, IN RE: ONGLYZA (SAXAGLIPTIN) AND KOMBIGLYZE XR (SAXAGLIPTIN AND METFORMIN) PRODUCTS LIABILITY LITIGATION.

[W]e find that these actions involve common questions of fact, and that centralization under Section 1407 in the Eastern District of Kentucky will serve the convenience of the parties and witnesses and promote the just and efficient conduct of this litigation. All actions share numerous factual questions, inasmuch as plaintiffs allege that the use of Onglyza or Kombiglyze XR caused them or their decedent to develop heart failure or other conditions such as congestive heart failure, myocardial infarction and/or cardiovascular injury.

According to that JPML Transfer Order the Defendants -- AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Co., and McKesson Corp. -- opposed centralization of approximately 80 Onglyza and Kombiglyze lawsuits into this new MDL:

Defendants oppose transfer by arguing that plaintiffs’ allegations are supported by a single study (the SAVOR study), which itself supports only claims regarding heart failure – not the various other injuries (congestive heart failure, acute hypoxic respiratory failure, coronary artery disease and cardiovascular injury) plaintiffs allege. They argue that, as a consequence, these cases likely will turn on unique issues that are applicable to, at most, a small subset of other cases. Defendants also assert that informal coordination among the actions is a feasible alternative to centralization. These objections are insufficient to overcome the significant advantages that centralization will afford.

Defendants concede that most cases involve allegations of heart failure, which is squarely in line with the results of the SAVOR study and the subsequent label change for Onglyza and Kombiglyze XR in April 2016. If defendants are convinced that plaintiffs’ claims regarding heart failure or other injuries lack scientific support, then centralization affords them a single forum in which to seek summary judgment, which might be applied to other similar cases.

As background, in April 2016 the FDA took regulatory action by mandating label changes with new warnings about an increased risk of heart failure for these relatively new diabetes medicines in the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs:

ISSUE: FDA is warning that the liver disease medicine Ocaliva (obeticholic acid) has been incorrectly dosed daily instead of weekly in patients with moderate to severe primary biliary cholangitis (PBC), a rare chronic liver disease, increasing the risk of serious liver injury. To ensure correct dosing and reduce the risk of liver problems, FDA is clarifying the current recommendations for screening, dosing, monitoring, and managing PBC patients with moderate to severe liver disease taking Ocaliva. FDA is adding a new Boxed Warning, FDA’s most prominent warning, to highlight this information in the prescribing information of the drug label. FDA is also requiring a Medication Guide for patients to inform them about this issue.

As a condition of approval, FDA required the manufacturer of Ocaliva, Intercept Pharmaceuticals, to continue studying the medicine in patients with advanced PBC. These clinical trials are currently ongoing and FDA expects to receive results in 2023. FDA is adding the additional warnings to the drug label after receiving reports that Ocaliva is being given to PBC patients with moderate to severe liver impairment more often than is recommended in the prescribing information, resulting in liver decompensation, liver failure, and sometimes death. FDA will continue to monitor this medicine and will update the public if new information becomes available.

BACKGROUND: This is an update to the MedWatch safety alert for Ocaliva (obeticholic acid) - Increased Risk of Serious Liver Injury, issued 09-21-2017.

• In postmarketing reports, hepatic decompensation and failure, in some cases fatal, have been reported in patients with primary biliary cholangitis (PBC) with decompensated cirrhosis or Child-Pugh Class B or C hepatic impairment when OCALIVA was dosed more frequently than recommended [see Warnings and Precautions (5.1)].

• The recommended starting dosage of OCALIVA is 5 mg once weekly for patients with Child-Pugh Class B or C hepatic impairment or a prior decompensation event [see Dosage and Administration (2.2)].

Ocaliva (obeticholic acid) is Intercept's sole marketed product, winning approval in May 2016 for a rare type of chronic liver disease known as primary biliary cholangitis or PBC. Few other treatments exist for the progressive disease, which can lead to cirrhosis and liver failure....

In September, the company issued a so-called "Dear Health Care Provider" letter warning of complications including liver failure and death when patients with moderate to severe PBC received higher-than-intended doses of Ocaliva. [Note: Added link to this Intercept Pharmaceuticals letter about Ocaliva dated 9/8/17.]

The FDA followed that up with a drug safety communication outlining similar concerns. By the regulator's tally, nineteen patients receiving Ocaliva died over the 13 months from the drug's launch through last September. Seven out of the eight fatal cases with available information on cause of death showed the patients had incorrectly received daily doses, instead of the weekly administration recommended for those with moderate to severe declines in liver function.

Lastly, according to Intercept Pharmaceutical’s February 1, 2018 press release, the company is also working with the European Medicines Agency to update the Ocaliva drug label in Europe and will issue a Direct Healthcare Professional Communication to educate physicians on the appropriate Ocaliva dosage for patients with advanced cirrhosis.

Saxenda Dose Contains Twice As Much Liraglutide As Diabetes Medicine Victoza, Also Linked To Malignancy In Pancreas

In 2014, the FDA approved Saxenda (liraglutide) for the treatment of obesity. Novo Nordisk is the responsible pharmaceutical company.

Liraglutide, the active ingredient for Saxenda, is a glucagonlike peptide-1 (GLP-1) receptor agonist. More generally, Saxenda is in the incretin mimetic class of drugs.

Four years earlier, the FDA approved another liraglutide-containing medicine, Victoza, which is a popular Type-2 diabetes drug.

Like Victoza, Saxenda has been associated with an increased risk of pancreatic cancer, or pancreas cancer, in patients using this still relatively new obesity, or weight-loss, drug.

However, the alarming difference between Saxenda and Victoza is that the standard dose of Saxenda for obesity contains 3.0 mg of liraglutide, while the standard doses of Victoza for diabetes are 1.2 mg or 1.8 mg of liraglutide. So the patient using Saxenda is getting about two-times more liraglutide than the patient using Victoza.

While the current Prescribing Information, or drug label, for Saxenda (accessed 1/30/18) has a so-called "Black-Box Warning" for the risk of thyroid C-cell tumors, a type of thyroid cancer, and pancreatitis is mentioned in the Warnings and Precautions section, there is nothing about an increased risk of pancreatic cancer.

Consider liraglutide, an injectable drug that works in part by helping the pancreas produce more insulin. The drug also suppresses appetite by fooling the brain into thinking the stomach is full.

Liraglutide is the generic name for Saxenda, which was approved for obesity in December. It is merely a higher dose of Victoza, a drug that has been marketed since 2010 for type 2 diabetes.

As a diabetes drug, Victoza was the primary suspect in 348 deaths and more than 3,100 hospitalizations through June 2014, according to the most recently available FDA data. At least 100 of those reported deaths were linked to pancreatic cancer....

With the approval of higher-dose Saxenda, the FDA doubled down on its confidence in the drug's safety. It has a 3-mg daily dose, compared with 1.2 mg or 1.8 mg for Victoza.

The labels for both drugs also warn patients to stop using the drugs promptly if pancreatitis is suspected.

That's what Tom LaRosa did last August when a blood test showed possible inflammation of his pancreas, said his wife, Sandy. The test was done because he had been having stomach problems, which can be a warning sign of pancreatic cancer.

LaRosa, 72, had been using the 1.8 mg dose of Victoza since 2010 to control his blood sugar with the hope it would also help him lose weight....

Despite stopping the use of Victoza in August, LaRosa's stomach problems got worse.

On Thanksgiving Day, the stomach pain was so severe that he went to the hospital. After a CT scan, he was diagnosed with pancreatic cancer.

He died in January.

Sandy LaRosa said her husband was never told that Victoza might increase his risk of pancreatic cancer. His doctor, Bradley Javorsky, MD, said he did tell LaRosa about the risks of pancreatitis and pancreatic cancer risk.

"I have that discussion with everybody," said Javorsky, an endocrinology and diabetes specialist and assistant professor with the Medical College of Wisconsin.

As stated above, today there is nothing about an increased risk of pancreatic cancer in the drug label for Saxenda, nor is there any such warning in the current Prescribing Information for Victoza (accessed 1/30/18).

While Dr. Javorsky may have talked with his patients about the pancreatic cancer risk of liraglutide back then, since there is no warning about pancreas cancer in either the current Saxenda or Victoza drug labels, it is unlikely that many doctors are having this discussion with their patients even today.

We are currently investigating pancreatic cancer cases involving Saxenda -- as well as Victoza and other incretin mimetic diabetes drugs such as Byetta, Bydureon, Januvia, and Janumet -- as drug injury lawsuits filed against the responsible pharmaceutical company based on this failure to warn about the increased risk of pancreatic cancer.

January 23, 2018

In 2017, Viberzi and Actemra were both identified as having significant adverse side effects. In fact, many have even died as a result of conditions caused by these drugs.

Looking forward into 2018, we will continue to monitor the medical and regulatory literature as well as conduct research concerning the harmful side effects of Viberzi and Actemra, and report on any significant developments.

Viberzi

Viberzi (eluxadoline) is a relatively new drug used to treat irritable bowel syndrome in adults when the main symptom is diarrhea (IBS-D).

It is usually taken daily in order to reduce diarrhea and abdominal pain, and acts directly in the intestine to decrease bowel contractions.

If you or some one you know used Viberzi and received a diagnosis of pancreatitis or Sphincter of Oddi spasm, then we encourage you to submit a Drug Injury Law Case Review – it is free, confidential, and there is no obligation.

Resources:

Actemra

Actemra (tocilizumab) is an injection approved by the FDA for the treatment of several different medical conditions:

Moderately to severely active rheumatoid arthritis in adult patients who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs);

Giant Cell Arteritis (GCA) in adult patients;

Polyarticular Juvenile Idiopathic Arthritis (PJIA) in patients 2 years of age and older; and,

Systemic Juvenile Idiopathic Arthritis (SJIA) in patients 2 years of age and older.

Potential Actemra Side Effects

According to the FDA, the following side effects have been observed among those using Actemra:

Pancreatitis

Heart Failure

Heart Attacks / Myocardial Infarction (MI)

Strokes (CVA)

Interstitial Lung Disease (ILD)

At this point in time, there seems to be a significant amount of evidence that Actemra may increase the risk of heart failure and pancreatitis. However, the FDA is still in the process of reviewing the "less convincing" evidence that it causes heart attacks, strokes, and ILD.

To date, they have yet to require these side effects to be added to the drug label.

If you or some one you know used Actemra and received a diagnosis of pancreatitis, heart failure, heart attack, stroke, or ILD, then we encourage you to submit a Drug Injury Law Case Review – it is free, confidential, and there is no obligation.

January 18, 2018

In 2017, the Mirena IUD and Ocaliva were both identified as having significant adverse side effects. Mirena IUD lawsuits have already been filed, and several people have lost their lives as a result of Ocaliva.

Looking forward into 2018, we will continue to monitor the medical and regulatory literature as well as conduct research concerning the harmful side effects of the Mirena IUD and Ocaliva, and report on any significant developments.

Mirena IUD

Mirena is an intrauterine device (IUD) that releases small amounts of a progestin hormone called levonorgestrel.

This hormone works to prevent pregnancy for up to five years through several processes that take place within the female reproductive system.

Potential Mirena IUD Side Effects

Apart from the more common Mirena IUD side effects such as migration of the device, perforation of the uterus, and embedment within the uterus, an additional harmful side effect was recently identified.

Pseudotumor cerebri (PTC), also referred to as idiopathic intracranial hypertension (IIH), is a condition that is caused by an accumulation of cerebrospinal fluid (CSF) in the skull. This excess of fluid creates pressure on the brain, which can lead to swollen optic nerves.

Unfortunately, the failure to timely diagnose and treat PTC / IIH may lead to permanent vision loss and even blindness.

However, diagnosing this condition is not as straightforward as one would hope. Patients experiencing the symptoms of PTC / IIH often first undergo an MRI, CT scan, and/or other diagnostic radiology tests to rule out an actual tumor or blood clot in the brain. A lumbar puncture, or spinal tap, may then be performed in order to confirm the diagnosis of PTC / IIH.

If you or some one you know used the Mirena IUD and received a diagnosis of PTC / IIH, or experienced the symptoms mentioned above, then we encourage you to submit aDrug Injury Law Case Review – it is free, confidential, and there is no obligation.

If you or some one you know used Ocaliva and received a diagnosis of drug-induced liver injury, liver failure, or death, then we encourage you to submit aDrug Injury Law Case Review – it is free, confidential, and there is no obligation.

This Relatively New Idiopathic Pulmonary Fibrosis (IPF) Pill Is Clearly On The Radar Of Drug Safety Regulators

OFEV (nintedanib) capsules were approved by the FDA in 2014 for treatment of idiopathic pulmonary fibrosis (IPF). Boehringer Ingelheim Pharmaceuticals, Inc. is the drug company responsible for OFEV in the US.

From the Background Information section of that new Health Canada document we get this overview of the safety issue:

OFEV (nintedanib) is used to treat idiopathic pulmonary fibrosis (IPF).

Cases of [drug-induced liver injury (DILI)] have been observed with OFEV treatment in the post-marketing setting since the product was launched in 2014. The overall cumulative [idiopathic pulmonary fibrosis (IPF)] patient exposure to OFEV from marketing experience is estimated to be over 32,000 patient-years. As of October 15, 2017, 32 cases of DILI have been reported worldwide in patients treated with OFEV, including one in Canada. In 24 of the 32 cases, the outcome of the DILI events was reported. In the majority (17) of these cases, the DILI event resolved when the dose was reduced or treatment was stopped. In 6 cases, the patient had not recovered at the time of reporting. One case resulted in fatal outcome.

That document went on to state "Health Canada is working with the manufacturer to update the Canadian Product Monograph [for OFEV] with this safety information."

Cases of drug-induced liver injury have been observed with OFEV treatment [see Adverse Reactions (6.2)]. In the post-marketing period, non-serious and serious cases of drug-induced liver injury, including severe liver injury with fatal outcome, have been reported. The majority of hepatic events occur within the first three months of treatment. In clinical trials, administration of OFEV was associated with elevations of liver enzymes (ALT, AST, ALKP, GGT) and bilirubin. Liver enzyme and bilirubin increases were reversible with dose modification or interruption in the majority of cases. The majority (94%) of patients with ALT and/or AST elevations had elevations <5 times ULN. The majority (95%) of patients with bilirubin elevations had elevations <2 times ULN [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]. Patients with a low body weight (<65 kg), Asian, and female patients may have a higher risk of elevations in liver enzymes. Nintedanib exposure increased with patient age, which may also result in a higher risk of increased liver enzymes [see Clinical Pharmacology (12.3)]. Conduct liver function tests (ALT, AST, and bilirubin) upon initiation of treatment with OFEV, at regular intervals during the first three months of treatment, and periodically thereafter or as clinically indicated. Dosage modifications or interruption may be necessary for liver enzyme elevations. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with OFEV, promptly interrupt therapy [see Dosage and Administration (2.1, 2.3)].

We will continue monitor the medical literature, FDA, and Health Canada for further developments regarding this drug-induced liver injury issue for OLEV.

January 05, 2018

At the Law Offices of Thomas J. Lamb, we are committed to providing up-to-date information on matters pertaining to drug injury law. Over the course of 2017, we have reviewed countless medical studies and journals, and reported the significant medical, legal, and regulatory developments through our two blogs.

Attorney Tom Lamb's blog, Drug Injury Watch, consists of articles related to serious side effects of prescription drugs, and major developments in some of the current drug litigations.

My blog, Drug Safety Developments,reports and elaborates on the information contained in medical and legal news concerning the safety of brand-name prescription drugs.

Below, I have provided an index of the articles published on the Drug Injury Watch blog in 2017. These articles are organized categorically, and listed in the following section. Click on the categories below to jump to that section of the page, then click on the title of the article to view it in full at its source.

In Comparison, This December 2017 Regulatory Action By FDA In The US: "new class warning... for all gadolinium-based contrast agents"

There seems to be a consensus among the United States FDA and the United Kingdom MHRA drug safety agencies that low levels of gadolinium can be retained in the brain and other tissues after administration of gadolinium-based contrast agents (GBCAs) for months to years after receiving these drugs.

Another point of agreement between those agencies is that certain linear GBCAs -- such as Magnevist, Omniscan, and OptiMARK -- result in more gadolinium retention in the body than macrocyclic GBCAs.

There is a difference, however, between FDA and MHRA in terms of the regulatory actions being taken with respect to this class of drugs, now.

There is currently no evidence that gadolinium deposition in the brain has caused adverse neurological effects in patients; however, licences for gadodiamide (Omniscan) and intravenous gadopentetic acid (also known as gadopentetate dimegulumine; Magnevist) will be suspended from 1 February 2018 and these products will be recalled.

Further, this MHRA document points out that "One linear agent, gadoversetamide (OptiMARK), has been withdrawn by the Marketing Authorisation Holder and is not available in the UK."

In comparison, at the present time FDA is only requiring that there be certain changes made to the Prescribing Information, or drug label, of all gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) in the US. To be clear, none of these products will be recalled from the market here.

To date, the only known adverse health effect related to gadolinium retention is a rare condition called nephrogenic systemic fibrosis (NSF) that occurs in a small subgroup of patients with pre-existing kidney failure. We have also received reports of adverse events involving multiple organ systems in patients with normal kidney function. A causal association between these adverse events and gadolinium retention could not be established.

We are continuing to assess the health effects of gadolinium retention in the body and will update the public when new information becomes available....

Accordingly, we will be watching for any future recommendations from the FDA's Medical Imaging Drugs Advisory Committee about further label changes or regulatory actions for gadolinium-based contrast agents, especially Magnevist, Omniscan, and OptiMARK, here in the US.

Reports Of Drug-Induced Liver Injury And Hypersensitivity Pneumonitis Are At Center Of This Unusual Drug Safety Controversy

... "We are not shipping. We're not promoting. We're not sampling doctors," said Primus President and CEO James Weir. "We have terminated all of those activities in good faith even though we don't believe our product is life threatening."

Primus sells Limbrel as a "medical food," but the FDA said last month that the product is an unapproved drug linked to 194 adverse events over the last decade.

Limbrel has not been recalled though the FDA has asked Primus to make a voluntary recall. Primus is waiting to obtain the documents on which FDA has based its safety alert and recall request prior to making a final decision, although the opinions of independent experts and the medical literature conflict with FDA’s safety alert and request for recall.

The U.S. Food and Drug Administration recommended that Primus Pharmaceuticals, Scottsdale, Arizona, voluntarily recall Limbrel, a capsule marketed to manage the metabolic processes associated with osteoarthritis. The company has not yet acted to remove the product from the market. Although the product is marketed as a medical food, the preliminary determination of the FDA investigation is that Limbrel is an unapproved new drug. The agency does not have mandatory recall authority over drug products.

The FDA reminds consumers not to use any Limbrel products because of the risk of drug-induced liver injury, and a lung condition called hypersensitivity pneumonitis. Consumers taking any Limbrel products should stop immediately and contact their health care provider. Health care providers who are aware that their patients are taking Limbrel should advise them to stop using it.

The FDA continues to investigate a rise in reports of serious adverse events, including drug-induced liver injury and a lung condition called hypersensitivity pneumonitis, involving Limbrel, a product in capsule form currently marketed to “manage the metabolic processes associated with osteoarthritis.”

On November 30, 2017, the FDA reiterated to Primus Pharmaceuticals the agency’s safety concerns and serious health risks associated with continued use of the product. The FDA recommended a voluntary recall, but so far the company has declined to take the product off the market.

The FDA is advising consumers not to use any Limbrel products because of the risk of drug-induced liver injury and a lung condition called hypersensitivity pneumonitis. If you are taking this product, discontinue it immediately and contact your health care provider. Health care providers who are aware that their patients are taking Limbrel should advise them to stop using it.

On that same FDA page, the next section, "What is the Problem and What is Being Done About It?", provides some additional information about this unfolding Limbrel situation:

On November 8, 2017, the FDA first contacted Primus Pharmaceuticals regarding the adverse events and requested information about the formula for Limbrel. The formula is being reviewed by the FDA. The FDA also obtained product samples from the company and the samples are undergoing testing.

The FDA continues to investigate Primus Pharmaceuticals and the manufacturing process for Limbrel, and will share updates as they become available.

We will continue to follow this developing drug safety issue. Further, we welcome anyone with insights to the Limbrel situation to post their information in a Comment below or share it with us privately by sending me an email.

Overall side effects and serious side effects were balanced between the Jardiance [(empagliflozin)] and placebo groups in adults with and without peripheral artery disease. In the group with peripheral artery disease, lower-limb amputations occurred in 5.5 percent of those treated with Jardiance and 6.3 percent of those treated with placebo. In the group without peripheral artery disease, lower-limb amputations occurred in 0.9 percent of those treated with Jardiance and 0.7 percent of those treated with placebo….

It includes this apparent "soft" disclaimer about the findings of those medical researchers whose names were displayed next to the article title.

We acknowledge the inherent limitations of manually identifying [lower limb amputation (LLA)] and performing post hoc analyses. A dedicated case report form was not used in the EMPA-REG OUTCOME trial as there was no concern regarding an increased risk of amputation with [Jardiance (empagliflozin)] before or during the trial. We are confident that the reporting and systematic retrieval processes employed were thorough.

Furthermore, and perhaps significantly, at the end of this Diabetes Care article text appears the following note:

Acknowledgments. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Elizabeth Ng of FleishmanHillard Fishburn, London, U.K., during the preparation of this paper.

We point out that there is a similar Acknowledgments note concerning the involvement of FleishmanHillard Fishburn at the end of the earlier-mentioned Circulation Research Letter, also.

[D]octors are clearly still concerned about this and whether it represents a class effect of SGLT2 inhibitors or is specific to [Invokana (canagliflozin)].

Commenting on the topic in a recent perspective for Medscape Medical News, Harpreet Bajaj of Mount Sinai Hospital, University of Toronto, Ontario, said: "To reassure us of the benefit/harm balance with [Invokana (canagliflozin)], we clinicians need more data-mining from CANVAS and additional long-term randomized controlled trials."

This Medscape story did not indicate whether Dr. Bajaj thought the Boehringer Ingelheim press release, the Diabetes Care article, or the Healio piece alleviated his own concerns, at least, about lower limb amputations possibly being associated with other SGLT2 inhibitors, like Jardiance and Farxiga.

However, that statement by Dr. Bajaj was immediately followed by this sub-headline for the next part of the November 27 Medscape story: Inherent Limitations in Manually Identifying Lower-Limb Amputations.

John Buse, the chief of endocrinology at UNC - Chapel Hill provided his opinion on the matter, "Personally, I would much rather have a small heart attack than lose a toe... And I think I would much rather have a big heart attack than lose a leg.” He anticipates a significant debate, saying that the benefits and harms are most likely "over- and under-estimated in each study." [emphasis added]

In closing, it appears there needs to more medical research done on the risk of lower limb amputations for patients who use the increasing popular diabetes medicines in this SGLT2 inhibitors drug class, which includes Invokana and Jardiance as well as Farxiga.

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